Hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by left ventricular hypertrophy. Mutations in genes for sarcomere proteins, e.g., in cardiac myosin-binding protein C (cMyBPC), may cause symptoms like heart failure and sudden cardiac death. In HCM, the heart utilizes high amounts of glucose. Increased glucose metabolism creates intermediates for hyaluronan (HA) synthesis, resulting in HA accumulation within the extracellular space, which could contribute to cardiomyocyte hypertrophy. We aimed to describe the connection between HA and cardiomyocyte hypertrophy using cMyBPC+/- mice treated with two different β-blockers - either metoprolol or propranolol - for 11 months. The results showed that HA metabolism is altered in HCM, and that HA is significantly more abundant in hearts of cMyBPC+/- mice compared to wild-type mice. Areas of high HA abundance were spread around the tissue in a 'patchy' manner. This focally increased HA concentration correlated with increased cardiomyocyte size in the same areas of the heart. Gene expression of HA synthase 2 was elevated in cMyBPC+/- mice. Treatment with propranolol maintained HA synthase 2 at wild-type level, while significantly increasing HA synthase 3 expression. However, treatment with metoprolol or propranolol did not prevent HA accumulation nor decreased cardiomyocyte hypertrophy. These novel findings visualise a spatial connection between high HA abundance and cardiomyocyte hypertrophy in the hearts of cMyBPC+/- mice.

AIMS:Cardiomyopathies are a heterogeneous group of genetic disorders requiring specialised, multidisciplinary management to optimize patient outcomes. A critical aspect of care is the transition of paediatric patients to adult services, which varies significantly across healthcare systems.This study assessed current practices in care transition and multidisciplinary management of inherited and rare cardiomyopathies across specialised European centres within the European Reference Network for rare and low prevalence complex diseases of the heart network. METHODS AND RESULTS:A 21-question survey was distributed to healthcare providers within the network. A single participant (i.e. cardiologist with expertise in the diagnosis and management of inherited and rare cardiomyopathies) from each centre was approached. Responses from 26 centres across 12 European countries were analysed using descriptive statistics to evaluate institutional characteristics, transition protocols, and multidisciplinary team involvement. While 81% of centres reported having a transition plan, only 42% implemented it for all patients, and 19% had no formal protocol. Multidisciplinary care was well integrated, with regular team discussions, though key professionals such as psychologists and nurses were often absent. The lack of structured transition programmes, inconsistent use of standardized protocols, and a shortage of specialists in cardiogenetics emerged as major unmet needs. CONCLUSION:Significant variability exists in the transition and multidisciplinary care of patients with inherited and rare cardiomyopathies. Standardized transition protocols, greater involvement of multiple healthcare professionals, and enhanced training in cardiogenetics are needed to ensure continuity of care and improve patient care across Europe.

Left (LAV) and right (RAV) atrial volumes are independent markers of cardiovascular risk in heart failure. Simultaneous assessment of myocardial blood flow (MBF) and atrial volumes might improve the clinical utility of cardiac PET. The aim of this study was to develop and validate an automated method for obtaining atrial volumes from dynamic myocardial perfusion PET scans without ECG-gating. The atria were segmented automatically using first-pass data from [15O]-water PET at rest, combining voxel-wise images of bolus area-under-curve and arrival time. Data of multiple patient cohorts were analyzed: retrospective method development in 36 subjects with systolic heart failure with prospective validation in 59 subjects with same-day echocardiograms (primary hypertrophic cardiomyopathy (n = 25), suspected or known cardiac amyloidosis (n = 25) and healthy controls (n = 9)). Test-retest repeatability of PET was assessed in clinical chest pain patients scanned twice on the same day (n = 15). Segmentation was successful in all scans (n=125). PET and echocardiography correlated for LAV in the development cohort (r=0.83, p<0.001) and in the validation cohort (LAV: r=0.83, RAV: r=0.77, both p<0.001). In alignment with echocardiography, PET identified statistically significant differences between healthy controls and subjects with hypertrophied hearts for LAV index: 26 (interquartile range: 24-29) versus 41 (32-51) ml/m2, p<0.001, and RAV index: 31 (25-43) versus 48 (38-61) ml/m2, p=0.003). Test-retest reproducibility was excellent for LAV (intraclass correlation coefficient ICC=0.96, repeatability coefficient RPC=8.6 ml/m2) and for RAV (ICC=0.96, RPC=11.6 ml/m2). Left and right atrial volumes can be extracted automatically, accurately and reproducibly using dynamic PET.

Abstract Background/Introduction Cardiomyopathies are common and affect up to 1:250 of the population. Despite conferring a risk for sudden cardiac death and substantial disease burdens that could be reduced through better awareness, detection and care, cardiomyopathy care is rarely incorporated in European and national health policies. New European Society of Cardiology cardiomyopathy guidelines (1) could substantially benefit care but need to be supported by effective policies. Cardiomyopathies Matter is a Europe-wide, multistakeholder initiative aiming to raise awareness about cardiomyopathies and to ensure they receive the policy attention they warrant from EU and national decision-makers. Methods Cardiomyopathies Matters participants include experts from the fields of cardiology, cardiac nursing, economics, and patient advocacy, coordinated by a Secretariat, representing 36 countries and 6 patient advocacy groups (PAGs). A Policy Roadmap and other publications were co-created based on i) reviews of published and grey literature, and ii) input from topic experts and PAGs through 2 group workshops, individual consultation meetings, and a modified nominal group technique reviewing successive drafts toward consensus approval. Results The Roadmap (2) identifies unmet needs and challenges throughout the patient care pathway and offers holistic EU and national policy recommendations to address these and improve patient outcomes (Figure 1). These include policy measures to support early and accurate diagnosis, access to expert multidisciplinary care, guidelines-informed disease investigation and management, holistic support and empowerment of patients and carers, and research and innovation. Key aspects for nurses and allied health professionals include the need for 1)improved knowledge and awareness to promote early diagnosis; 2)rapid referral systems to multidisciplinary care and access to specialist cardiomyopathy or heart failure nurses care coordination, 3)genetic counselling (index cases and cascade/family screening), and 4)support of patients and families. Building on existing examples of good practice at national expert centre networks (e.g. France, Spain, UK),Cardiomyopathies Matter published updated policy recommendations for the European Union mandate (3), which are now being adopted more widely. National initiatives are underway or in development in Belgium, Hungary, Italy, Netherlands, Poland, and Spain. Local actions include multistakeholder roundtables and events, national Roadmap publications, events, educational activities, and media outreach. Conclusions EU and national Cardiovascular Health Action Plans are needed, with specific attention to cardiomyopathies and other inherited CVDs. Cardiomyopathies Matter fosters collaboration between healthcare professionals, PAGs and policymakers to promote policies that ensure all patients and families have access to guidelines-informed care.Figure 1Cardiomyopathy Priorities

To develop a method for diagnosing left ventricular (LV) hypertrophy from cardiac perfusion 15O-water positron emission tomography (PET). We retrospectively pooled data from 139 subjects in four research cohorts. LV remodeling patterns ranged from normal to severe eccentric and concentric hypertrophy. 15O-water PET scans (n = 197) were performed with three different PET devices. A low-end scanner (66 scans) was used for method development, and remaining scans with newer devices for a blinded evaluation. Dynamic data were converted into parametric images of perfusable tissue fraction for semi-automatic delineation of the LV wall and calculation of LV mass (LVM) and septal wall thickness (WT). LVM and WT from PET were compared to cardiac magnetic resonance (CMR, n = 47) and WT to 2D-echocardiography (2DE, n = 36). PET accuracy was tested using linear regression, Bland–Altman plots, and ROC curves. Observer reproducibility were evaluated using intraclass correlation coefficients. High correlations were found in the blinded analyses (r ≥ 0.87, P < 0.0001 for all). AUC for detecting increased LVM and WT (> 12 mm and > 15 mm) was ≥ 0.95 (P < 0.0001 for all). Reproducibility was excellent (ICC ≥ 0.93, P < 0.0001). 15O-water PET might detect LV hypertrophy with high accuracy and precision.

Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference.  In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.

Introduction Hypertrophic cardiomyopathy (HCM) is a common disorder with various manifestations, including sudden cardiac death. Patients with suspected or confirmed HCM may be encountered throughout the healthcare system, especially in internal medicine and cardiology. Thus, thorough knowledge of HCM is essential among healthcare providers. Methods A web-based questionnaire was developed to assess the cross-sectional evaluation of HCM knowledge. It covered aspects such as epidemiology and diagnosis, treatment, lifestyle, risk stratification of sudden cardiac death, and implantable cardioverter-defibrillator knowledge. Results In total, 123 subjects completed the survey. The mean age was 38.5 ±10.7 years and two-thirds (n=82) were females; 43.1% were physicians (non-specialist 24.4%, cardiologists 8.9%, specialist, other than cardiology 9.8%); and the remaining were nurses (nurses within cardiology 37.4%, nurses outside cardiology 19.5%). Almost all subjects had heard about the disease (95.9%) and the vast majority (77.2%) had taken part in the management of a patient with HCM. The total mean score was 15.9 ±3.9 credits and the 25th, 50th, and 75th percentiles were 14, 15, and 18 credits, respectively. The predefined arbitrary pass score of ≥60% was reached by 61.8%, and 20.3% were considered to pass with distinction. Physicians scored higher than nurses (70.7 ±17.0% vs 58.1 ±11.8; p<0.001). Within each professional category, there was a similar score with regard to gender. Conclusions There is a considerable lack of knowledge of HCM among healthcare professionals working within the field of internal medicine/cardiology. This insufficient knowledge may contribute to less implementation of evidence-based medicine and current guidelines, although further studies are needed to confirm this.

Background: The objectives of the study were to describe positron emission tomography (PET) parameters, using the tracers O-15-water at rest/stress, C-11-acetate, and C-11-HED, with regard to nonsustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy (HCM). PET offers quantitative assessment of pathophysiology throughout the left ventricular segments, including the endocardium/epicardium. The potential use PET in risk stratification remains to be elucidated. NSVT provides a marker for sudden cardiac death. Methods: Patients with a validated diagnosis of HCM who had an implantable cardioverter-defibrillator were interrogated at 12 months and independently of PET-examinations. Results: In total, 25 patients (mean age 56.8 +/- 12.9 years, 76% males) were included and 10 reported NSVT. Mean myocardial blood flow (MBF) at rest was 0.91 ml/g/min and decreased at stress, 1.59 ml/ g/min. The mean gradient (endocardium/epicardium quotient) at rest was 1.14 +/- 0.09, while inverse at stress (mean 0.92 +/- 0.16). Notably, MBF gradient at stress was significantly lower in patients with NSVT (p = 0.022) and borderline at rest (p = 0.059) while global MBF at rest and stress were not. Mean myocardial oxygen consumption (MVO2) was 0.088 ml/g/min (higher in NSVT, p = 0.023) and myocardial external efficiency 18.5%. Using C-11-HED, the mean retention index was 0.11 min (1) and a higher volume of distribution (p = 0.089) or transmural gradient of clearance rate (p = 0.061) or lower clearance rate (p = 0.052) showed a tendency of association of NSVT. Conclusions: The endocardium/epicardium MBF gradient at stress is significantly lower in HCM patients with NSVT. This provides a novel approach to further refine risk stratification of sudden cardiac death. (C) 2019 The Authors. Published by Elsevier B.V.

PurposeStringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.MethodsWe compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes—rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.ResultsRare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10−18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10−13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.ConclusionLarge case–control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Surgical myectomy (SM) and alcohol septal ablation (ASA) are two invasive therapies for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM), despite medical therapy. This meta-analysis aims to compare the efficacy of the two procedures. We searched all electronic databases until February 2020 for clinical trials and cohorts comparing clinical outcomes of ASA and SM treatment of patients with HOCM. The primary endpoint was all-cause mortality, cardiovascular (CV) mortality, sudden cardiac death (SCD), re-intervention, and complications. Secondary endpoints included relief of clinical symptoms and drop of left ventricular outflow tract (LVOT) gradient. Twenty studies (4547 patients; 2 CTs and 18 cohorts) comparing ASA vs. SM with a mean follow-up of 47 ± 28.7 months were included. Long term (8.72 vs. 7.84%, p = 0.42) and short term (1.12 vs. 1.27%, p = 0.93) all-cause mortality, CV mortality (2.48 vs. 3.66%, p = 0.26), SCD (1.78 vs. 0.76%, p = 0.20) and stroke (0.36 vs. 1.01%, p = 0.64) were not different between procedures. ASA was associated with lower peri-procedural complications (5.57 vs. 10.5%, p = 0.04) but higher rate of re-interventions (10.1 vs. 0.27%; p < 0.001) and pacemaker dependency (12.4 vs. 4.31%, p = 0.0004) compared to SM. ASA resulted in less reduction in LVOT gradient (−47.8 vs. −58.4 mmHg, p = 0.01) and less improvement of clinical symptoms compared to SM (New York Heart Association (NYHA) class III/IV, 82.4 vs. 94.5%, p < 0.001, angina 53.2 vs. 84.2%, p = 0.02). Thus, ASA and SM treatment of HOCM carry a similar risk of mortality. Peri-procedural complications are less in alcohol ablation but re-intervention and pacemaker implantations are more common. These results might impact the procedure choice in individual patients, for the best clinical outcome.

BACKGROUND:Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease associated with arrhythmias. Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death and part of the current risk stratification. Furthermore, atrial fibrillation (AF), which increases the risk of stroke, is believed to be common in HCM patients. Routine ambulatory monitoring captures the rhythm only periodically over 24-48 h; thus, the true burden of arrhythmia is unknown. The insertable cardiac monitor (ICM) should help determine a more realistic arrhythmia assessment in HCM patients.OBJECTIVE:The purpose of this study was to ascertain the incidence of NSVT, AF, and bradycardia in unselected HCM patients by the use of an ICM.METHODS:Thirty adults, mean age 49.9 ± 12.3 years, 25 (83.3%) males were implanted with a Confirm Rx ICM. The monitoring application was installed on the patient's smartphone, which allowed for patient activation in case of symptoms. The ICM was programmed as follows: ventricular tachycardia (VT) ≥ 160 beats per minute (bpm) for ≥8 intervals, AF ≥ 2 min of duration, and bradycardia ≤ 40 bpm or pause ≥ 3.0 s.RESULTS:The mean calculated 5-year risk was 2.3%, and 29/30 of the patients had a risk <4%. During follow-up, AF was found in nine patients (30.0%). At least one episode of NSVT was detected in seven patients (23.3%). In 13 patients (43.3%), sinoatrial block/sinus arrest/sinus bradycardia were seen. No arrhythmia was detected in nine patients (30.0%).CONCLUSION:In this first prospective study using an ICM, the arrhythmia burden in HCM patients yielded 30.0% AF and 23.3% NSVT.

OBJECTIVES:N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. METHODS:We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. RESULTS:Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). CONCLUSIONS:MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

During the development of hypertrophic cardiomyopathy, the heart returns to fetal energy metabolism where cells utilize more glucose instead of fatty acids as a source of energy. Metabolism of glucose can increase synthesis of the extracellular glycosaminoglycan hyaluronan, which has been shown to be involved in the development of cardiac hypertrophy and fibrosis. The aim of this study was to investigate hyaluronan metabolism in cardiac tissue from patients with hypertrophic cardiomyopathy in relation to cardiac growth. NMR and qRT-PCR analysis of human cardiac tissue from hypertrophic cardiomyopathy patients and healthy control hearts showed dysregulated glucose and hyaluronan metabolism in the patients. Gas phase electrophoresis revealed a higher amount of low molecular mass hyaluronan and larger cardiomyocytes in cardiac tissue from patients with hypertrophic cardiomyopathy. Histochemistry showed high concentrations of hyaluronan around individual cardiomyocytes in hearts from hypertrophic cardiomyopathy patients. Experimentally, we could also observe accumulation of low molecular mass hyaluronan in cardiac hypertrophy in a rat model. In conclusion, the development of hypertrophic cardiomyopathy with increased glucose metabolism affected both hyaluronan molecular mass and amount. The process of regulating cardiomyocyte size seems to involve fragmentation of hyaluronan.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease with regard to clinical manifestations. It is characterized by an asymmetric pattern of hypertrophy of the left ventricle. However, less is known about pathophysiological distribution of the abnormalities. Positron emission tomography (PET) provides quantitative assessment of myocardial blood flow (MBF), oxidative metabolism, and sympathetic innervation using the following tracers: 15O-water, 11C-acetate, and 11C-HED. The purpose of the present study was to investigate if physiological parameters measured with PET are more impaired in hypertrophic regions compared to non-hypertrophic regions. We examined 25 HCM patients using a Discovery MI PET/CT with 15O-water, 11C-acetate, and 11C-HED. Wall thickness (WT) was calculated from the 11C-acetate scan for basal and mid segments (n=12) in the 17-segment model and hypertrophic regions were defined as segments >15 mm. 15O-water PET was performed during rest and adenosine induced stress. Quantification of MBF, oxygen consumption (MVO2) and retention index of 11C-HED (RIHED) was done in aQuant software. Comparison of parameters in hypertrophic regions to non-hypertrophic regions was done using Mann-Whitney U- test and Bland-Altman analysis with repeatability coefficient defined as 2 times the standard-deviation of differences. One patient had all segments >15mm and one patient had all segments <15mm and were therefore excluded from analysis. WT was 18.2±1.9 mm in hypertrophic regions and 12.2±1.5 mm in non-hypertrophic regions. None of the PET-parameters showed a significant difference between hypertrophic and non-hypertrophic regions, see table 1. Table 1 MBFREST MBFSTRESS MVO2 RIHED Hypertrophic segments (mm) 0.70±0.20 1.74±0.92 0.092±0.026 0.12±0.037 Non-hypertrophic segments (mm) 0.68±0.18 1.71±0.87 0.094±0.025 0.12±0.036 p-value 0.767 0.851 0.956 0.684 Repeatability coefficient (%) 25.4 35.4 13.3 16.2 Mean ± standard deviation for PET-parameters in hypertrophic and non-hypertrophic segments. Relative repeatability coefficient (%) between regions and p-value for Mann-Whitney U-test. Pathophysiology in terms of myocardial blood flow at rest and stress, oxygen consumption and sympathetic innervation are not significantly different in hypertrophic segments compared to non-hypertrophic segments in patients with HCM. Thus, the disease is not confined to hypertrophied areas but spread throughout the left ventricle. Selanders stiftelse, Regionala forskningsrådet

Abstract Background Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease associated with arrhythmias. Life-threatening ventricular tachycardia (VT) or fibrillation is the main cause of sudden cardiac death (SCD) in HCM, even though bradycardia does occur. An implantable cardioverter-defibrillator effectively prevents SCD. Non-sustained VT is a risk factor for SCD and part of current risk stratification. Furthermore, atrial fibrillation (AF) is believed to be common in HCM and increases the risk of stroke. Notably, novel oral anticoagulant (NOAC) is recommended in HCM with AF, even in the absence of other risk factors. Routinely, arrhythmias are evaluated by 24–48 hours of ambulatory monitoring occasionally. Thus, the true burden of arrhythmia is unknown but may be elucidated by an insertable cardiac monitor (ICM). Purpose The purpose of this study was to ascertain the incidence of NSVT, AF, and significant bradycardia in unselected HCM patients by use of an ICM. Methods In total, 30 adults with HCM had an ICM Confirm Rx implanted subcutaneously at the level of the fourth rib on the left side. None had a cardiac device implanted previously since they were considered to be at low risk for SCD according to ESC risk score. The application for monitoring was installed in the patients' phone which also allowed for patient activation in case of symptoms. The ICM was programmed as follows: VT ≥160 beats per minute (bpm) during ≥8 intervals, AF ≥2minute of duration, and bradycardia ≤40 bpm or pause ≥3.0 s. Clin Trial Reg: NCT03259113. Results In total, 29 patients, mean age 51.2±12.3 years, 24 (82.8%) males, completed the monitoring and 1 had the phone disconnected the vast majority of time and was excluded for analyses. During a follow-up of 14–18 months, 9 patients (31.0%) had AF and were started on NOAC and potential dose-adjustment of beta-blocker. One of these patients had syncope due to rapidly conducted AF. One of the patients with AF also had episodes of atrial flutter. At least one episode of NSVT was detected in 6 patients (20.7%). In 11 patients (37.9%), sino-atrial block/sinus arrest were seen, typically 30–40 bpm. In 9 patients (31.0%) no significant arrhythmia were detected. Conclusion In this first study of ICM in HCM, evaluation of arrhythmia burden in low risk patients with HCM, yielded 31.0% AF, 20.7% NSVT, and 37.9% sino-atrial block/arrest. Acknowledgement/Funding Abbott

Calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischaemia, despite potential discrepancy in its expression pattern compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic aetiology for it. In a pilot study we studied three candidate genes, ENPP1, ABCC6 and NTE5 which may predispose to coronary arterial or valvular calcification. We studied 65 patients with CCAD and 5 patients with calcific aortic valve disease (CAVD). Five DNA variants potentially affecting protein function were found in six patients. Our findings support genetic variants might influence the development of CCAD and CAVD, however, segregation in the families must first be performed to ascertain any damaging effect of these variants. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes.

Extensive coronary calcification without significant stenosis, described as calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischemia. There is a discrepancy in the expression pattern of CCAD compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic etiology for it.In this pilot study we studied 3 candidate genes, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1), ATP Binding Cassette Subfamily C Member 6 (ABCC6), and 5'-Nucleotidase Ecto (NT5E) involved in pyrophosphate (PPi) and inorganic phosphate (Pi) metabolism, which may predispose to coronary arterial or valvular calcification. We studied 70 patients with calcific cardiac disease; 65 with CCAD (age 43-83 years) and 5 with calcific aortic valve disease (CAVD) (age 76-82 years).Five DNA variants potentially affecting protein function were found in 6 patients. One variant is a known disease-causing mutation in the ABCC6 gene. Our findings support that disturbances in the PPi and Pi metabolism might influence the development of CCAD and CAVD. However, segregation in the families must first be performed to ascertain any damaging effect of these variants we have found.We report 4 new genetic variants potentially related to coronary calcification, through the disturbed Pi and PPi metabolism. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes particularly those involved with Pi and PPi metabolism.

Elevation of troponin reflects myocardial infarction. The underlying causes should be assessed, as treatment and prognosis may differ widely. Myocardial damage with non-obstructive coronary arteries requires further evaluation including magnetic resonance tomography. We report a case of significant myocardial ischemia which was unnoticed by myocardial scintigraphy but detected by positron emission tomography (PET). The 15O-water tracer allows for quantitative assessment of myocardial perfusion including regional abnormalities and may thus diagnose microvascular dysfunction.

Intensive participation in sport has positive physiological effects on the heart. The contractility of the heart improves, the ejection fraction increases and the muscle mass of the heart increases, thus leading to a greater cardiac output. Despite these positive effects, there is still an increased risk for acute cardiac events and an increase in cardiac muscle mass induced by sports is not always beneficial. It may cause a thickening of interventricular septum in course of hypertrophic cardiomyopathy or be a source of arrhythmia. The workload of the heart can be very high in some sports and may in some cases be the reason for sudden cardiac death. In these cases, there is often an underlying heart disease (cardiomyopathy) unknown before the actual event. Electrocardiographic examination (ECG) may reveal some of these diseases but although ECG examinations can be a useful tool to discover pathological conditions, there could be difficulties in interpreting different ECG patterns, especially in athletes. In some cases, athletes may exhibit ECG patterns that are similar to those in heart diseases such as cardiomyopathies (QRS-amplitudes, ST-segment elevation and T wave inversions in lateral leads). This pattern is even more common in athletes of African origins. Furthermore, cardiomyopathies such as hypertrophic cardiomyopathy (HCM) are more common among athletes with African heritage than in white athletes. Thus correct interpretation of ECG is crucial for several reasons: to distinguish between benign physiological (‘athlete’s heart’) and pathological changes, to lower the risk of sudden cardiac death, and to save time and money by not undertaking further examination of the heart.